Pantetheine phosphorylation

The resulting 2-benzylthioethylamine could be debenzylated by treatment with sodium in liquid ammonia. However, when 2-benzylthioethylamine was treated with carbobenzyloxy-P-alanine azide (prepared from carbobenzyloxy-P-alanylhydrazide by nitrosation), 2-benzylthio-7V-(carbobenzyloxy-P-alanyl)ethyl-amine formed. Reduction with sodium in liquid ammonia was sufficient to remove both the benzyl and carbobenzyloxy protecting groups and, as noted above, reaction with pantolactone yielded pantetheine. Phosphorylation to the mono- and diphosphates of pantetheine has been effected with the corresponding dibenzylphospho-nates (vide supra, ATP). 

One of the alternative activities of PanK enzymes that have only recently been formally characterized is their ability to phosphorylate the advanced CoA biosynthetic intermediate, pantetheine 12 (Equation (3)). 

Coenzyme A is a complex organic molecule with a nucleotide portion of adenine, ribose and phosphoryl groups linked through a pyrophosphoryl bridge to an unusual peptide, pantetheine. This structure has a branched-chain dihydroxy acid, pantoic acid, linked to /3-aIanine which in turn is bonded to thioethylamine. In spite of the complexity of the coenzyme A... 

The various enrymes of this adenylate-forming family catalyze a set of reactions, including (a) phosphoryl-group-mediated cleavage of adenylates with substrate release, and (b) aminoacylation of CoA- or protein-bound pantetheine. The first set of reactions includes the substrate-dependent isotope exchange leaccion... 

Pantothenic acid is not synthesized by the body and therefore must be obtained from the diet. It is condensed with a molecule of cysteine and the resulting pseudopeptide is decarboxylated to form a compound of pantothenic acid and thioethanolamine, pantetheine. The latter, in the presence of ATP and a phosphokinase, becomes phosphopantatheine, which, in the presence of ATP and a pyrophosphorylase, is converted to dephospho-CoA, which, in turn, is phosphorylated on the 3 position of ribose in the presence of ATP and a phosphokinase to form CoA (Fig. 78). 

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